Neuroscience

Articles and news from the latest research reports.

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Clouds in the Head: New Model of Brain’s Thought Processes A new model of the brain’s thought processes explains the apparently chaotic activity patterns of individual neurons. They do not correspond to a simple stimulus/response linkage, but arise from the networking of different neural circuits. Scientists funded by the Swiss National Science Foundation (SNSF) propose that the field of brain research should expand its focus. Many brain researchers cannot see the forest for the trees. When they use electrodes to record the activity patterns of individual neurons, the patterns often appear chaotic and difficult to interpret. “But when you zoom out from looking at individual cells, and observe a large number of neurons instead, their global activity is very informative,” says Mattia Rigotti, a scientist at Columbia University and New York University who is supported by the SNSF and the Janggen-Pöhn-Stiftung. Publishing in Nature together with colleagues from the United States, he has shown that these difficult-to-interpret patterns in particular are especially important for complex brain functions. What goes on in the heads of apes The researchers have focussed their attention on the activity patterns of 237 neurons that had been recorded some years previously using electrodes implanted in the frontal lobes of two rhesus monkeys. At that time, the apes had been taught to recognise images of different objects on a screen. Around one third of the observed neurons demonstrated activity that Rigotti describes as “mixed selectivity.” A mixed selective neuron does not always respond to the same stimulus (the flowers or the sailing boat on the screen) in the same way. Rather, its response differs as it also takes account of the activity of other neurons. The cell adapts its response according to what else is going on in the ape’s brain. Chaotic patterns revealed in context Just as individual computers are networked to create concentrated processing and storage capacity in the field of Cloud Computing, links in the complex cognitive processes that take place in the prefrontal cortex play a key role. The greater the density of the network in the brain, in other words the greater the proportion of mixed selectivity in the activity patterns of the neurons, the better the apes were able to recall the images on the screen, as demonstrated by Rigotti in his analysis. Given that the brain and cognitive capabilities of rhesus monkeys are similar to those of humans, mixed selective neurons should also be important in our own brains. For him this is reason enough why brain research from now on should no longer be satisfied with just the simple activity patterns, but should also consider the apparently chaotic patterns that can only be revealed in context.

Clouds in the Head: New Model of Brain’s Thought Processes

A new model of the brain’s thought processes explains the apparently chaotic activity patterns of individual neurons. They do not correspond to a simple stimulus/response linkage, but arise from the networking of different neural circuits. Scientists funded by the Swiss National Science Foundation (SNSF) propose that the field of brain research should expand its focus.

Many brain researchers cannot see the forest for the trees. When they use electrodes to record the activity patterns of individual neurons, the patterns often appear chaotic and difficult to interpret. “But when you zoom out from looking at individual cells, and observe a large number of neurons instead, their global activity is very informative,” says Mattia Rigotti, a scientist at Columbia University and New York University who is supported by the SNSF and the Janggen-Pöhn-Stiftung. Publishing in Nature together with colleagues from the United States, he has shown that these difficult-to-interpret patterns in particular are especially important for complex brain functions.

What goes on in the heads of apes

The researchers have focussed their attention on the activity patterns of 237 neurons that had been recorded some years previously using electrodes implanted in the frontal lobes of two rhesus monkeys. At that time, the apes had been taught to recognise images of different objects on a screen. Around one third of the observed neurons demonstrated activity that Rigotti describes as “mixed selectivity.” A mixed selective neuron does not always respond to the same stimulus (the flowers or the sailing boat on the screen) in the same way. Rather, its response differs as it also takes account of the activity of other neurons. The cell adapts its response according to what else is going on in the ape’s brain.

Chaotic patterns revealed in context

Just as individual computers are networked to create concentrated processing and storage capacity in the field of Cloud Computing, links in the complex cognitive processes that take place in the prefrontal cortex play a key role. The greater the density of the network in the brain, in other words the greater the proportion of mixed selectivity in the activity patterns of the neurons, the better the apes were able to recall the images on the screen, as demonstrated by Rigotti in his analysis. Given that the brain and cognitive capabilities of rhesus monkeys are similar to those of humans, mixed selective neurons should also be important in our own brains. For him this is reason enough why brain research from now on should no longer be satisfied with just the simple activity patterns, but should also consider the apparently chaotic patterns that can only be revealed in context.

Filed under neurons neural activity prefrontal cortex cognitive function primates neuroscience science

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Finding a family for a pair of orphan receptors in the brain Researchers at Emory University have identified a protein that stimulates a pair of “orphan receptors” found in the brain, solving a long-standing biological puzzle and possibly leading to future treatments for neurological diseases. The results are published in the Proceedings of the National Academy of Sciences, Early Edition. The human genome is littered with orphans: proteins that look like they will bind and respond to a hormone or a brain chemical, based on the similarity of their sequences to other proteins. However, scientists haven’t figured out what each orphan’s partner chemical is yet. Orphans that look like GPCRs (G protein-coupled receptors) currently number about 100. GPCRs are the targets of many drugs and are involved in vision, smell and brain cells’ responses to a host of hormones and neurotransmitters. One orphan GPCR, called GPR37, has attracted interest from researchers because it is connected with an inherited form of Parkinson’s disease. It is abundant in the dopamine-producing neurons that degenerate in Parkinson’s. But its partner chemical, or “ligand,” has not been found. "We reasoned that GPR37 had to be doing something important, besides becoming misfolded in some forms of Parkinson’s," says senior author Randy Hall, PhD, professor of pharmacology at Emory University School of Medicine. Working with Hall, graduate student Rebecca Meyer devised a way to detect when cells producing GPR37 were reacting with GPR37’s ligand. "Usually, cells remove GPCRs from their surfaces when they encounter their ligand," Meyer says. "So we set things up so that GPR37 would be labeled red on the surface of the cell, but would appear green once internalized." They discovered that cells producing GPR37 – and also a close relative, GPR37L1 — respond to a protein known as prosaposin, which was discovered by John O’Brien of University of California San Diego in the 1990s. Prosaposin is a growth factor for brain cells and protects them from stress. Scientists studying it had worked out that it stimulates cells via a GPCR – but which one was unclear until now. In animal models, prosaposin has shown potential for treating conditions such as stroke, Parkinson’s and neuropathic pain. An artificial fragment of prosaposin called prosaptide has been tested in clinical studies, but it quickly breaks down in the body. "That’s the reason why it was so important to find the receptor," Hall says. "Then we can actually do some pharmacology." Now, Hall’s laboratory is planning to look for other compounds that can activate GPR37 as well. These could be more stable in the body than the previously studied protein fragment and thus better potential drugs. Doctors have reported a few cases of genetic deficiency in prosaposin, leading to severe neurodegeneration. Mice engineered to lack GPR37 have more subtle brain perturbations, so Hall also plans to test the hypothesis that prosaposin acts by both GPR37 and GPR37L1, by “knocking out” both in mice, potentially duplicating the same severe effects seen in the human cases of prosaposin deficiency.

Finding a family for a pair of orphan receptors in the brain

Researchers at Emory University have identified a protein that stimulates a pair of “orphan receptors” found in the brain, solving a long-standing biological puzzle and possibly leading to future treatments for neurological diseases.

The results are published in the Proceedings of the National Academy of Sciences, Early Edition.

The human genome is littered with orphans: proteins that look like they will bind and respond to a hormone or a brain chemical, based on the similarity of their sequences to other proteins. However, scientists haven’t figured out what each orphan’s partner chemical is yet.

Orphans that look like GPCRs (G protein-coupled receptors) currently number about 100. GPCRs are the targets of many drugs and are involved in vision, smell and brain cells’ responses to a host of hormones and neurotransmitters. One orphan GPCR, called GPR37, has attracted interest from researchers because it is connected with an inherited form of Parkinson’s disease. It is abundant in the dopamine-producing neurons that degenerate in Parkinson’s. But its partner chemical, or “ligand,” has not been found.

"We reasoned that GPR37 had to be doing something important, besides becoming misfolded in some forms of Parkinson’s," says senior author Randy Hall, PhD, professor of pharmacology at Emory University School of Medicine.

Working with Hall, graduate student Rebecca Meyer devised a way to detect when cells producing GPR37 were reacting with GPR37’s ligand.

"Usually, cells remove GPCRs from their surfaces when they encounter their ligand," Meyer says. "So we set things up so that GPR37 would be labeled red on the surface of the cell, but would appear green once internalized."

They discovered that cells producing GPR37 – and also a close relative, GPR37L1 — respond to a protein known as prosaposin, which was discovered by John O’Brien of University of California San Diego in the 1990s.

Prosaposin is a growth factor for brain cells and protects them from stress. Scientists studying it had worked out that it stimulates cells via a GPCR – but which one was unclear until now. In animal models, prosaposin has shown potential for treating conditions such as stroke, Parkinson’s and neuropathic pain. An artificial fragment of prosaposin called prosaptide has been tested in clinical studies, but it quickly breaks down in the body.

"That’s the reason why it was so important to find the receptor," Hall says. "Then we can actually do some pharmacology."

Now, Hall’s laboratory is planning to look for other compounds that can activate GPR37 as well. These could be more stable in the body than the previously studied protein fragment and thus better potential drugs.

Doctors have reported a few cases of genetic deficiency in prosaposin, leading to severe neurodegeneration. Mice engineered to lack GPR37 have more subtle brain perturbations, so Hall also plans to test the hypothesis that prosaposin acts by both GPR37 and GPR37L1, by “knocking out” both in mice, potentially duplicating the same severe effects seen in the human cases of prosaposin deficiency.

Filed under neurological disorders brain cells receptors proteins ligands neuroscience science

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Reducing caloric intake delays nerve cell loss Activating an enzyme known to play a role in the anti-aging benefits of calorie restriction delays the loss of brain cells and preserves cognitive function in mice, according to a study published in the May 22 issue of The Journal of Neuroscience. The findings could one day guide researchers to discover drug alternatives that slow the progress of age-associated impairments in the brain. Previous studies have shown that reducing calorie consumption extends the lifespan of a variety of species and decreases the brain changes that often accompany aging and neurodegenerative diseases such as Alzheimer’s. There is also evidence that caloric restriction activates an enzyme called Sirtuin 1 (SIRT1), which studies suggest offers some protection against age-associated impairments in the brain. In the current study, Li-Huei Tsai — director of the Picower Institute for Learning and Memory and Picower Professor of Neuroscience at MIT — along with postdoc Johannes Gräff and others at MIT tested whether reducing caloric intake would delay the onset of nerve cell loss that is common in neurodegenerative disease, and if so, whether SIRT1 activation was driving this effect. The group not only confirmed that caloric restriction delays nerve cell loss, but also found that a drug that activates SIRT1 produces the same effects. “There has been great interest in finding compounds that mimic the benefits of caloric restriction that could be used to delay the onset of age-associated problems and/or diseases,” says Dr. Luigi Puglielli, who studies aging at the University of Wisconsin, Madison, and was not involved in this study. “If proven safe for humans, this study suggests such a drug could be used as a preventive tool to delay the onset of neurodegeneration associated with several diseases that affect the aging brain.” In the study, Tsai’s team first decreased the normal diets of mice genetically engineered to rapidly undergo changes in the brain associated with neurodegeneration by 30 percent. Following three months on the diet, the mice completed several learning and memory tests. “We not only observed a delay in the onset of neurodegeneration in the calorie-restricted mice, but the animals were spared the learning and memory deficits of mice that did not consume reduced-calorie diets,” Tsai says. Curious if they could recreate the benefits of caloric restriction without changing the animals’ diets, the scientists gave a separate group of mice a drug that activates SIRT1. Similar to what the researchers found in the mice exposed to reduced-calorie diets, the mice that received the drug had less cell loss and better cellular connectivity than the mice that did not receive the drug. Additionally, the mice that received the drug treatment performed as well as normal mice in learning and memory tests. “The question now is whether this type of treatment will work in other animal models, whether it’s safe for use over time, and whether it only temporarily slows down the progression of neurodegeneration or stops it altogether,” Tsai says.

Reducing caloric intake delays nerve cell loss

Activating an enzyme known to play a role in the anti-aging benefits of calorie restriction delays the loss of brain cells and preserves cognitive function in mice, according to a study published in the May 22 issue of The Journal of Neuroscience. The findings could one day guide researchers to discover drug alternatives that slow the progress of age-associated impairments in the brain.

Previous studies have shown that reducing calorie consumption extends the lifespan of a variety of species and decreases the brain changes that often accompany aging and neurodegenerative diseases such as Alzheimer’s. There is also evidence that caloric restriction activates an enzyme called Sirtuin 1 (SIRT1), which studies suggest offers some protection against age-associated impairments in the brain.

In the current study, Li-Huei Tsai — director of the Picower Institute for Learning and Memory and Picower Professor of Neuroscience at MIT — along with postdoc Johannes Gräff and others at MIT tested whether reducing caloric intake would delay the onset of nerve cell loss that is common in neurodegenerative disease, and if so, whether SIRT1 activation was driving this effect. The group not only confirmed that caloric restriction delays nerve cell loss, but also found that a drug that activates SIRT1 produces the same effects.

“There has been great interest in finding compounds that mimic the benefits of caloric restriction that could be used to delay the onset of age-associated problems and/or diseases,” says Dr. Luigi Puglielli, who studies aging at the University of Wisconsin, Madison, and was not involved in this study. “If proven safe for humans, this study suggests such a drug could be used as a preventive tool to delay the onset of neurodegeneration associated with several diseases that affect the aging brain.”

In the study, Tsai’s team first decreased the normal diets of mice genetically engineered to rapidly undergo changes in the brain associated with neurodegeneration by 30 percent. Following three months on the diet, the mice completed several learning and memory tests. “We not only observed a delay in the onset of neurodegeneration in the calorie-restricted mice, but the animals were spared the learning and memory deficits of mice that did not consume reduced-calorie diets,” Tsai says.

Curious if they could recreate the benefits of caloric restriction without changing the animals’ diets, the scientists gave a separate group of mice a drug that activates SIRT1. Similar to what the researchers found in the mice exposed to reduced-calorie diets, the mice that received the drug had less cell loss and better cellular connectivity than the mice that did not receive the drug. Additionally, the mice that received the drug treatment performed as well as normal mice in learning and memory tests.

“The question now is whether this type of treatment will work in other animal models, whether it’s safe for use over time, and whether it only temporarily slows down the progression of neurodegeneration or stops it altogether,” Tsai says.

Filed under calorie restriction nerve cells neurodegenerative diseases aging animal model cell loss neuroscience science

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Common Food Supplement Fights Degenerative Brain Disorders

Nutritional supplement delays advancement of Parkinson’s and Familial Dysautonomia, TAU researchers discover

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Widely available in pharmacies and health stores, phosphatidylserine is a natural food supplement produced from beef, oysters, and soy. Proven to improve cognition and slow memory loss, it’s a popular treatment for older people experiencing memory impairment. Now a team headed by Prof. Gil Ast and Dr. Ron Bochner of Tel Aviv University’s Department of Human Molecular Genetics has discovered that the same supplement improves the functioning of genes involved in degenerative brain disorders, including Parkinson’s disease and Familial Dysautonomia (FD).

In FD, a rare genetic disorder that impacts the nervous system and appears almost exclusively in the Ashkenazi Jewish population, a genetic mutation prevents the brain from manufacturing healthy IKAP proteins — which likely have a hand in cell migration and aiding connections between nerves — leading to the early degeneration of neurons. When the supplement was applied to cells taken from FD patients, the gene function improved and an elevation in the level of IKAP protein was observed, reports Prof. Ast. These results were replicated in a second experiment which involved administering the supplement orally to mouse populations with FD.

The findings, which have been published in the journal Human Molecular Genetics, are very encouraging, says Prof. Ast. “That we see such an effect on the brain — the most important organ in relation to this disease — shows that the supplement can pass through the blood-brain barrier even when administered orally, and accumulate in sufficient amounts in the brain.”

Slowing the death of nerve cells

Already approved for use as a supplement by the FDA, phosphatidylserine contains a molecule essential for transmitting signals between nerve cells in the brain. Prof. Ast and his fellow researchers decided to test whether the same chemical, which is naturally synthesized in the body and known to boost memory capability, could impact the genetic mutation which leads to FD.

Researchers applied a supplement derived from oysters, provided by the Israeli company Enzymotec, to cells collected from FD patients. Noticing a robust effect on the gene, including a jump in the production of healthy IKAP proteins, they then tested the same supplement on mouse models of FD, engineered with the same genetic mutation that causes the disease in humans.

The mice received the supplement orally, every two days for a period of three months. Researchers then conducted extensive genetic testing to assess the results of the treatment. “We found a significant increase of the protein in all the tissues of the body,” reports Prof. Ast, including an eight-fold increase in the liver and 1.5-fold increase in the brain. “While the food supplement does not manufacture new nerve cells, it probably delays the death of existing ones,” he adds.

Therapeutic potential for Parkinson’s

That the supplement is able to improve conditions in the brain, even when given orally, is a significant finding, notes Prof. Ast. Most medications enter the body through the blood stream, but are incapable of breaking through the barrier between the blood and the brain.

In addition, the researchers say the supplement’s positive effects extend beyond the production of IKAP. Not only did phosphatidylserine impact the gene associated with FD, but it also altered the level of a total of 2400 other genes — hundreds of which have been connected to Parkinson’s disease in previous studies.

The researchers believe that the supplement may have a beneficial impact on a number of degenerative diseases of the brain, concludes Prof. Ast, including a major potential for the development of new medications which would help tens of millions of people worldwide suffering from these devastating diseases.

(Source: aftau.org)

Filed under parkinson's disease familial dysautonomia memory impairment genetic mutations nerve cells food supplement neuroscience science

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B vitamins could delay dementia Despite spending billions of dollars on research and development, drug companies have been unable to come up with effective treatments for dementia and Alzheimer’s Disease (AD). Now, A. David Smith at the University of Oxford and his colleagues have discovered that, in some patients experiencing mild cognitive impairment (MCI), a cocktail of high-dose B vitamins could prevent gray matter loss associated with progression to AD. The study appears in the Proceedings of the National Academy of Sciences. The World Health Organization predicts that between 2010 and 2050 the number of dementia cases will increase from 26 million to 115 million worldwide. Although there is an urgent demand for treatment, pharmaceutical companies have been unable to develop drugs that will delay or cure dementia. So far, approved drugs merely ease symptoms. Smith and his team wanted to see if B vitamins reduced the risk of AD by lowering total homocysteine (tHcy) levels. There is a positive correlation between high tHcy levels and risk of cognitive impairment and AD. The researchers studied 156 subjects over 70 in Oxford, England who suffered from MCI. The subjects received either a placebo or a high-dose B vitamin cocktail consisting of 20 milligrams of vitamin B6, 0.5 milligrams of vitamin B12 and 0.8 milligrams of folic acid. Over a two-year period, subjects in both the experimental and control groups lost gray matter in the medial temporal, lateral temporoparietal and occipital regions and in the anterior and posterior cingulate cortex. However, those receiving B vitamin treatment experienced significantly less atrophy in regions of the brain most affected in people with AD and people with MCI who go on to develop AD. These include the bilateral hippocampus, the parahippocampal gyrus, the retrosplenial precuneus, the lingual gyrus, the fusiform gyrus and the cerebellum. The placebo group experienced a 3.7 percent loss of gray matter in these regions, compared with a 0.5 percent loss among the experimental group. When they looked at baseline tHcy levels, Smith and his colleagues found that B-vitamin treatment did not significantly reduce gray matter atrophy among subjects with tHcy levels below the median. The B-vitamin cocktail did have a significant effect on high-tHcy participants: those receiving the cocktail experienced only a 0.6 percent loss of gray matter, while high-tHcy participants in the placebo group experienced a 5.2 percent loss. The team found a correlation between gray matter loss and worsening of scores on tests that measure cognitive function. A causal Bayesian network analysis showed that B vitamins lower tHcy levels. This decreases gray matter atrophy, which delays cognitive decline.

B vitamins could delay dementia

Despite spending billions of dollars on research and development, drug companies have been unable to come up with effective treatments for dementia and Alzheimer’s Disease (AD). Now, A. David Smith at the University of Oxford and his colleagues have discovered that, in some patients experiencing mild cognitive impairment (MCI), a cocktail of high-dose B vitamins could prevent gray matter loss associated with progression to AD. The study appears in the Proceedings of the National Academy of Sciences.

The World Health Organization predicts that between 2010 and 2050 the number of dementia cases will increase from 26 million to 115 million worldwide. Although there is an urgent demand for treatment, pharmaceutical companies have been unable to develop drugs that will delay or cure dementia. So far, approved drugs merely ease symptoms.

Smith and his team wanted to see if B vitamins reduced the risk of AD by lowering total homocysteine (tHcy) levels. There is a positive correlation between high tHcy levels and risk of cognitive impairment and AD.

The researchers studied 156 subjects over 70 in Oxford, England who suffered from MCI. The subjects received either a placebo or a high-dose B vitamin cocktail consisting of 20 milligrams of vitamin B6, 0.5 milligrams of vitamin B12 and 0.8 milligrams of folic acid.

Over a two-year period, subjects in both the experimental and control groups lost gray matter in the medial temporal, lateral temporoparietal and occipital regions and in the anterior and posterior cingulate cortex.

However, those receiving B vitamin treatment experienced significantly less atrophy in regions of the brain most affected in people with AD and people with MCI who go on to develop AD. These include the bilateral hippocampus, the parahippocampal gyrus, the retrosplenial precuneus, the lingual gyrus, the fusiform gyrus and the cerebellum. The placebo group experienced a 3.7 percent loss of gray matter in these regions, compared with a 0.5 percent loss among the experimental group.

When they looked at baseline tHcy levels, Smith and his colleagues found that B-vitamin treatment did not significantly reduce gray matter atrophy among subjects with tHcy levels below the median. The B-vitamin cocktail did have a significant effect on high-tHcy participants: those receiving the cocktail experienced only a 0.6 percent loss of gray matter, while high-tHcy participants in the placebo group experienced a 5.2 percent loss.

The team found a correlation between gray matter loss and worsening of scores on tests that measure cognitive function.

A causal Bayesian network analysis showed that B vitamins lower tHcy levels. This decreases gray matter atrophy, which delays cognitive decline.

Filed under alzheimer's disease B vitamins cognitive impairment gray matter brain neuroscience science

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Drugs found to both prevent and treat Alzheimer’s disease in mice Researchers at USC have found that a class of pharmaceuticals can both prevent and treat Alzheimer’s Disease in mice. The drugs, known as “TSPO ligands,” are currently used for certain types of neuroimaging. "We looked at the effects of TSPO ligand in young adult mice when pathology was at an early stage, and in aged mice when pathology was quite severe," said lead researcher Christian Pike of the USC Davis School of Gerontology. "TSPO ligand reduced measures of pathology and improved behavior at both ages." The team’s findings were published online by the Journal of Neuroscience on May 15. Pike’s coauthors include USC postdoctoral scientists Anna M. Barron, Anusha Jayaraman and Joo-Won Lee; as well as Donatella Caruso and Roberto C. Melcangi of the University of Milan and Luis M. Garcia-Segura of the Instituto Cajal in Spain. The most surprising finding for Pike and his team was the effect of TSPO ligand in the aged mice. Four treatments—once per week over four weeks—in older mice resulted in a significant decrease of Alzheimer’s-related symptoms and improvements in memory – meaning that TSPO ligands may actually reverse some elements of Alzheimer’s disease. "Our data suggests the possibility of drugs that can prevent and treat Alzheimer’s," Pike said. "It’s just mouse data, but extremely encouraging mouse data. There is a strong possibility that TSPO ligands similar to the ones used in our study could be evaluated for therapeutic efficacy in Alzheimer’s patients within the next few years." Next, the team will next focus on understanding how TSPO ligands reduce Alzheimer’s disease pathology. Building on the established knowledge that TSPO ligands can reduce inflammation—shielding nerve cells from injury and increasing the production of neuroactive hormones in the brain—the team will study which of these actions is the most significant in fighting Alzheimer’s disease so they can develop newer TSPO ligands accordingly.

Drugs found to both prevent and treat Alzheimer’s disease in mice

Researchers at USC have found that a class of pharmaceuticals can both prevent and treat Alzheimer’s Disease in mice.

The drugs, known as “TSPO ligands,” are currently used for certain types of neuroimaging.

"We looked at the effects of TSPO ligand in young adult mice when pathology was at an early stage, and in aged mice when pathology was quite severe," said lead researcher Christian Pike of the USC Davis School of Gerontology. "TSPO ligand reduced measures of pathology and improved behavior at both ages."

The team’s findings were published online by the Journal of Neuroscience on May 15. Pike’s coauthors include USC postdoctoral scientists Anna M. Barron, Anusha Jayaraman and Joo-Won Lee; as well as Donatella Caruso and Roberto C. Melcangi of the University of Milan and Luis M. Garcia-Segura of the Instituto Cajal in Spain.

The most surprising finding for Pike and his team was the effect of TSPO ligand in the aged mice. Four treatments—once per week over four weeks—in older mice resulted in a significant decrease of Alzheimer’s-related symptoms and improvements in memory – meaning that TSPO ligands may actually reverse some elements of Alzheimer’s disease.

"Our data suggests the possibility of drugs that can prevent and treat Alzheimer’s," Pike said. "It’s just mouse data, but extremely encouraging mouse data. There is a strong possibility that TSPO ligands similar to the ones used in our study could be evaluated for therapeutic efficacy in Alzheimer’s patients within the next few years."

Next, the team will next focus on understanding how TSPO ligands reduce Alzheimer’s disease pathology. Building on the established knowledge that TSPO ligands can reduce inflammation—shielding nerve cells from injury and increasing the production of neuroactive hormones in the brain—the team will study which of these actions is the most significant in fighting Alzheimer’s disease so they can develop newer TSPO ligands accordingly.

Filed under alzheimer's disease ligands animal model nerve cells neuroactive hormones neuroscience science

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Waiting for a sign? Researchers find potential brain ‘switch’ for new behavior You’re standing near an airport luggage carousel and your bag emerges on the conveyor belt, prompting you to spring into action. How does your brain make the shift from passively waiting to taking action when your bag appears? A new study from investigators at the University of Michigan and Eli Lilly may reveal the brain’s “switch” for new behavior. They measured levels of a neurotransmitter called acetylcholine, which is involved in attention and memory, while rats monitored a screen for a signal. At the end of each trial, the rat had to indicate if a signal had occurred. Researchers noticed that if a signal occurred after a long period of monitoring or “non-signal” processing, there was a spike in acetylcholine in the rat’s right prefrontal cortex. No such spike occurred for another signal occurring shortly afterwards. "In other words, the increase in acetylcholine seemed to activate or ‘switch on’ the response to the signal, and to be unnecessary if that response was already activated," said Cindy Lustig, one of the study’s senior authors and an associate professor in the U-M Department of Psychology. The researchers repeated the study in humans using functional magnetic resonance imaging (fMRI), which measures brain activity, and also found a short increase in right prefrontal cortex activity for the first signal in a series. To connect the findings between rats and humans, they measured changes in oxygen levels, similar to the changes that produce the fMRI signal, in the brains of rats performing the task. They again found a response in the right prefrontal cortex that only occurred for the first signal in a series. A follow-up experiment showed that direct stimulation of brain tissue using drugs that target acetylcholine receptors could likewise produce these changes in brain oxygen. Together, the studies’ results provide some of the most direct evidence, so far, linking a specific neurotransmitter response to changes in brain activity in humans. The findings could guide the development of better treatments for disorders in which people have difficulty switching out of current behaviors and activating new ones. Repetitive behaviors associated with obsessive-compulsive disorder and autism are the most obvious examples, and related mechanisms may underlie problems with preservative behavior in schizophrenia, dementia and aging. The findings appear in the current issue of Journal of Neuroscience.

Waiting for a sign? Researchers find potential brain ‘switch’ for new behavior

You’re standing near an airport luggage carousel and your bag emerges on the conveyor belt, prompting you to spring into action. How does your brain make the shift from passively waiting to taking action when your bag appears?

A new study from investigators at the University of Michigan and Eli Lilly may reveal the brain’s “switch” for new behavior. They measured levels of a neurotransmitter called acetylcholine, which is involved in attention and memory, while rats monitored a screen for a signal. At the end of each trial, the rat had to indicate if a signal had occurred.

Researchers noticed that if a signal occurred after a long period of monitoring or “non-signal” processing, there was a spike in acetylcholine in the rat’s right prefrontal cortex. No such spike occurred for another signal occurring shortly afterwards.

"In other words, the increase in acetylcholine seemed to activate or ‘switch on’ the response to the signal, and to be unnecessary if that response was already activated," said Cindy Lustig, one of the study’s senior authors and an associate professor in the U-M Department of Psychology.

The researchers repeated the study in humans using functional magnetic resonance imaging (fMRI), which measures brain activity, and also found a short increase in right prefrontal cortex activity for the first signal in a series.

To connect the findings between rats and humans, they measured changes in oxygen levels, similar to the changes that produce the fMRI signal, in the brains of rats performing the task.

They again found a response in the right prefrontal cortex that only occurred for the first signal in a series. A follow-up experiment showed that direct stimulation of brain tissue using drugs that target acetylcholine receptors could likewise produce these changes in brain oxygen.

Together, the studies’ results provide some of the most direct evidence, so far, linking a specific neurotransmitter response to changes in brain activity in humans. The findings could guide the development of better treatments for disorders in which people have difficulty switching out of current behaviors and activating new ones. Repetitive behaviors associated with obsessive-compulsive disorder and autism are the most obvious examples, and related mechanisms may underlie problems with preservative behavior in schizophrenia, dementia and aging.

The findings appear in the current issue of Journal of Neuroscience.

Filed under brain activity prefrontal cortex brain tissue oxygen levels acetylcholine psychology neuroscience science

95 notes

UCSB Study Shows Where Scene Context Happens in our Brain In a remote fishing community in Venezuela, a lone fisherman sits on a cliff overlooking the southern Caribbean Sea. This man –– the lookout –– is responsible for directing his comrades on the water, who are too close to their target to detect their next catch. Using abilities honed by years of scanning the water’s surface, he can tell by shadows, ripples, and even the behavior of seabirds, where the fish are schooling, and what kind of fish they might be, without actually seeing the fish. This, in turn, changes where the boats go, and how the men fish. Though a seemingly simple and intuitive strategy, the lookout’s visual search function –– a process that takes mere seconds for the human brain –– is still something that a computer, despite technological advances, can’t do as accurately. "Behind what seems to be automatic is a lot of sophisticated machinery in our brain," said Miguel Eckstein, professor in UC Santa Barbara’s Department of Psychological & Brain Sciences. "A great part of our brain is dedicated to vision." Over the millennia of human evolution, our brains developed a pattern of search based largely on environmental cues and scene context. It’s an ability that has not only helped us find food and avoid danger in humankind’s earliest days, but continues to aid us today, in tasks as banal as driving to work, or shopping; or as specialized as reading X-rays. Where this –– the search for objects using scene and other objects –– occurs in the brain is little understood, and is for the first time discussed in the paper, “Neural Representations of Contextual Guidance in Visual Search of Real-World Scenes,” published recently in the Journal of Neuroscience. The researchers flashed hundreds images of indoor and outdoor scenes before observers, and instructed them to search for certain objects that were consistent with those scenes. Half of the images, however, did not contain the target object. During the trials, the subjects were asked to indicate whether the target object was present in the scene. The researchers were particularly interested in the images that did not contain the target. Another measure was taken to determine where subjects expected specific objects to be in target-absent scenes. Invariably, the subjects would indicate similar areas: If presented with a living room scene and told to look for a clock or a painting, they would indicate the wall; if shown a photo of a bathroom and told to indicate where to expect a hand soap or toothbrush, they would indicate the sink. The searched object’s contextual location in the scenes, according to the study, is represented in the area called the lateral occipital complex (LOC), a place that corresponds roughly to the lower back portion of the head, toward the side. This area, according to Eckstein, has the ability to account for other objects in the scene that often appear in close spatial proximity with the searched object –– something computers are only recently being taught to do. "So, if you’re looking for a computer mouse on a cluttered desk, a machine would be looking for things shaped like a mouse. It might find it, but it might see other objects of similar shape, and classify that as a mouse," Eckstein said. Computer vision systems might also not associate their target with specific locations or other objects. So, to a machine, the floor is just as likely a place for a mouse as a desk. The LOC, on the other hand, would contain the information the brain needs to direct a person’s attention and gaze first toward the most likely place that a mouse might be, such as on top of the desk, or near the keyboard. From there, other visual parts of the brain go to work, searching for particular characteristics, or determining the target’s presence. So strong is the scene context in biasing search, said Eckstein, that if another similar-looking object was placed in the location where the mouse is likely to be, and that scene briefly flashed before your eyes, you would likely –– erroneously –– interpret that object as the mouse. While scene context information has been found highly active in the LOC, other visual areas of the brain are also influenced by context to certain degrees, including the interparietal sulcus, located near the top of the head; and the retrosplenial cortex, found in the brain’s interior. "Since contextual guidance is a critical strategy that allows humans to rapidly find objects in scenes, studying the brain areas involved in normal humans might help us to gain a better understanding of neural areas involved in those with visual search deficits, such as brain-damaged patients and the elderly," Eckstein said. "Also, a large component of becoming an expert searcher –– like radiologists or fishermen –– is exploiting contextual relationships to search. Thus, understanding the neural basis of contextual guidance might allow us to gain a better understanding about what brain areas are critical to gain search expertise."

UCSB Study Shows Where Scene Context Happens in our Brain

In a remote fishing community in Venezuela, a lone fisherman sits on a cliff overlooking the southern Caribbean Sea. This man –– the lookout –– is responsible for directing his comrades on the water, who are too close to their target to detect their next catch. Using abilities honed by years of scanning the water’s surface, he can tell by shadows, ripples, and even the behavior of seabirds, where the fish are schooling, and what kind of fish they might be, without actually seeing the fish. This, in turn, changes where the boats go, and how the men fish.

Though a seemingly simple and intuitive strategy, the lookout’s visual search function –– a process that takes mere seconds for the human brain –– is still something that a computer, despite technological advances, can’t do as accurately.

"Behind what seems to be automatic is a lot of sophisticated machinery in our brain," said Miguel Eckstein, professor in UC Santa Barbara’s Department of Psychological & Brain Sciences. "A great part of our brain is dedicated to vision."

Over the millennia of human evolution, our brains developed a pattern of search based largely on environmental cues and scene context. It’s an ability that has not only helped us find food and avoid danger in humankind’s earliest days, but continues to aid us today, in tasks as banal as driving to work, or shopping; or as specialized as reading X-rays.

Where this –– the search for objects using scene and other objects –– occurs in the brain is little understood, and is for the first time discussed in the paper, “Neural Representations of Contextual Guidance in Visual Search of Real-World Scenes,” published recently in the Journal of Neuroscience.

The researchers flashed hundreds images of indoor and outdoor scenes before observers, and instructed them to search for certain objects that were consistent with those scenes. Half of the images, however, did not contain the target object. During the trials, the subjects were asked to indicate whether the target object was present in the scene.

The researchers were particularly interested in the images that did not contain the target. Another measure was taken to determine where subjects expected specific objects to be in target-absent scenes. Invariably, the subjects would indicate similar areas: If presented with a living room scene and told to look for a clock or a painting, they would indicate the wall; if shown a photo of a bathroom and told to indicate where to expect a hand soap or toothbrush, they would indicate the sink.

The searched object’s contextual location in the scenes, according to the study, is represented in the area called the lateral occipital complex (LOC), a place that corresponds roughly to the lower back portion of the head, toward the side. This area, according to Eckstein, has the ability to account for other objects in the scene that often appear in close spatial proximity with the searched object –– something computers are only recently being taught to do.

"So, if you’re looking for a computer mouse on a cluttered desk, a machine would be looking for things shaped like a mouse. It might find it, but it might see other objects of similar shape, and classify that as a mouse," Eckstein said. Computer vision systems might also not associate their target with specific locations or other objects. So, to a machine, the floor is just as likely a place for a mouse as a desk.

The LOC, on the other hand, would contain the information the brain needs to direct a person’s attention and gaze first toward the most likely place that a mouse might be, such as on top of the desk, or near the keyboard. From there, other visual parts of the brain go to work, searching for particular characteristics, or determining the target’s presence.

So strong is the scene context in biasing search, said Eckstein, that if another similar-looking object was placed in the location where the mouse is likely to be, and that scene briefly flashed before your eyes, you would likely –– erroneously –– interpret that object as the mouse.

While scene context information has been found highly active in the LOC, other visual areas of the brain are also influenced by context to certain degrees, including the interparietal sulcus, located near the top of the head; and the retrosplenial cortex, found in the brain’s interior.

"Since contextual guidance is a critical strategy that allows humans to rapidly find objects in scenes, studying the brain areas involved in normal humans might help us to gain a better understanding of neural areas involved in those with visual search deficits, such as brain-damaged patients and the elderly," Eckstein said. "Also, a large component of becoming an expert searcher –– like radiologists or fishermen –– is exploiting contextual relationships to search. Thus, understanding the neural basis of contextual guidance might allow us to gain a better understanding about what brain areas are critical to gain search expertise."

Filed under visual search lateral occipital complex contextual guidance psychology neuroscience science

145 notes

Mediterranean diet seems to boost ageing brain power A Mediterranean diet with added extra virgin olive oil or mixed nuts seems to improve the brain power of older people better than advising them to follow a low-fat diet, indicates research published online in the Journal of Neurology Neurosurgery and Psychiatry. The authors from the University of Navarra in Spain base their findings on 522 men and women aged between 55 and 80 without cardiovascular disease but at high vascular risk because of underlying disease/conditions. These included either type 2 diabetes or three of the following: high blood pressure; an unfavourable blood fat profile; overweight; a family history of early cardiovascular disease; and being a smoker. Participants, who were all taking part in the PREDIMED trial looking at how best to ward off cardiovascular disease, were randomly allocated to a Mediterranean diet with added olive oil or mixed nuts or a control group receiving advice to follow the low-fat diet typically recommended to prevent heart attack and stroke A Mediterranean diet is characterised by the use of virgin olive oil as the main culinary fat; high consumption of fruits, nuts, vegetables and pulses; moderate to high consumption of fish and seafood; low consumption of dairy products and red meat; and moderate intake of red wine. Participants had regular check-ups with their family doctor and quarterly checks on their compliance with their prescribed diet. After an average of 6.5 years, they were tested for signs of cognitive decline using a Mini Mental State Exam and a clock drawing test, which assess higher brain functions, including orientation, memory, language, visuospatial and visuoconstrution abilities and executive functions such as working memory, attention span, and abstract thinking. At the end of the study period, 60 participants had developed mild cognitive impairment: 18 on the olive oil supplemented Mediterranean diet; 19 on the diet with added mixed nuts; and 23 on the control group. A further 35 people developed dementia: 12 on the added olive oil diet; six on the added nut diet; and 17 on the low fat diet. The average scores on both tests were significantly higher for those following either of the Mediterranean diets compared with those on the low fat option. These findings held true irrespective of other influential factors, including age, family history of cognitive impairment or dementia, the presence of ApoE protein—associated with Alzheimer’s disease—educational attainment, exercise levels, vascular risk factors; energy intake and depression. The authors acknowledge that their sample size was relatively small, and that because the study involved a group at high vascular risk, it doesn’t necessarily follow that their findings are applicable to the general population. But they say, theirs is the first long term trial to look at the impact of the Mediterranean diet on brain power, and that it adds to the increasing body of evidence suggesting that a high quality dietary pattern seems to protect cognitive function in the ageing brain.

Mediterranean diet seems to boost ageing brain power

A Mediterranean diet with added extra virgin olive oil or mixed nuts seems to improve the brain power of older people better than advising them to follow a low-fat diet, indicates research published online in the Journal of Neurology Neurosurgery and Psychiatry.

The authors from the University of Navarra in Spain base their findings on 522 men and women aged between 55 and 80 without cardiovascular disease but at high vascular risk because of underlying disease/conditions.

These included either type 2 diabetes or three of the following: high blood pressure; an unfavourable blood fat profile; overweight; a family history of early cardiovascular disease; and being a smoker.

Participants, who were all taking part in the PREDIMED trial looking at how best to ward off cardiovascular disease, were randomly allocated to a Mediterranean diet with added olive oil or mixed nuts or a control group receiving advice to follow the low-fat diet typically recommended to prevent heart attack and stroke

A Mediterranean diet is characterised by the use of virgin olive oil as the main culinary fat; high consumption of fruits, nuts, vegetables and pulses; moderate to high consumption of fish and seafood; low consumption of dairy products and red meat; and moderate intake of red wine.

Participants had regular check-ups with their family doctor and quarterly checks on their compliance with their prescribed diet.

After an average of 6.5 years, they were tested for signs of cognitive decline using a Mini Mental State Exam and a clock drawing test, which assess higher brain functions, including orientation, memory, language, visuospatial and visuoconstrution abilities and executive functions such as working memory, attention span, and abstract thinking.

At the end of the study period, 60 participants had developed mild cognitive impairment: 18 on the olive oil supplemented Mediterranean diet; 19 on the diet with added mixed nuts; and 23 on the control group.

A further 35 people developed dementia: 12 on the added olive oil diet; six on the added nut diet; and 17 on the low fat diet.

The average scores on both tests were significantly higher for those following either of the Mediterranean diets compared with those on the low fat option.

These findings held true irrespective of other influential factors, including age, family history of cognitive impairment or dementia, the presence of ApoE protein—associated with Alzheimer’s disease—educational attainment, exercise levels, vascular risk factors; energy intake and depression.

The authors acknowledge that their sample size was relatively small, and that because the study involved a group at high vascular risk, it doesn’t necessarily follow that their findings are applicable to the general population.

But they say, theirs is the first long term trial to look at the impact of the Mediterranean diet on brain power, and that it adds to the increasing body of evidence suggesting that a high quality dietary pattern seems to protect cognitive function in the ageing brain.

Filed under mediterranean diet brain cognitive function aging cardiovascular disease neuroscience science

469 notes

Practice makes perfect? Not so much Turns out, that old “practice makes perfect” adage may be overblown. New research led by Michigan State University’s Zach Hambrick finds that a copious amount of practice is not enough to explain why people differ in level of skill in two widely studied activities, chess and music. In other words, it takes more than hard work to become an expert. Hambrick, writing in the research journal Intelligence, said natural talent and other factors likely play a role in mastering a complicated activity. “Practice is indeed important to reach an elite level of performance, but this paper makes an overwhelming case that it isn’t enough,” said Hambrick, associate professor of psychology. The debate over why and how people become experts has existed for more than a century. Many theorists argue that thousands of hours of focused, deliberate practice is sufficient to achieve elite status. Hambrick disagrees. “The evidence is quite clear,” he writes, “that some people do reach an elite level of performance without copious practice, while other people fail to do so despite copious practice.” Hambrick and colleagues analyzed 14 studies of chess players and musicians, looking specifically at how practice was related to differences in performance. Practice, they found, accounted for only about one-third of the differences in skill in both music and chess. So what made up the rest of the difference? Based on existing research, Hambrick said it could be explained by factors such as intelligence or innate ability, and the age at which people start the particular activity. A previous study of Hambrick’s suggested that working memory capacity – which is closely related to general intelligence – may sometimes be the deciding factor between being good and great. While the conclusion that practice may not make perfect runs counter to the popular view that just about anyone can achieve greatness if they work hard enough, Hambrick said there is a “silver lining” to the research. “If people are given an accurate assessment of their abilities and the likelihood of achieving certain goals given those abilities,” he said, “they may gravitate toward domains in which they have a realistic chance of becoming an expert through deliberate practice.”

Practice makes perfect? Not so much

Turns out, that old “practice makes perfect” adage may be overblown.

New research led by Michigan State University’s Zach Hambrick finds that a copious amount of practice is not enough to explain why people differ in level of skill in two widely studied activities, chess and music.

In other words, it takes more than hard work to become an expert. Hambrick, writing in the research journal Intelligence, said natural talent and other factors likely play a role in mastering a complicated activity.

“Practice is indeed important to reach an elite level of performance, but this paper makes an overwhelming case that it isn’t enough,” said Hambrick, associate professor of psychology.

The debate over why and how people become experts has existed for more than a century. Many theorists argue that thousands of hours of focused, deliberate practice is sufficient to achieve elite status.

Hambrick disagrees.

“The evidence is quite clear,” he writes, “that some people do reach an elite level of performance without copious practice, while other people fail to do so despite copious practice.”

Hambrick and colleagues analyzed 14 studies of chess players and musicians, looking specifically at how practice was related to differences in performance. Practice, they found, accounted for only about one-third of the differences in skill in both music and chess.

So what made up the rest of the difference?

Based on existing research, Hambrick said it could be explained by factors such as intelligence or innate ability, and the age at which people start the particular activity. A previous study of Hambrick’s suggested that working memory capacity – which is closely related to general intelligence – may sometimes be the deciding factor between being good and great.

While the conclusion that practice may not make perfect runs counter to the popular view that just about anyone can achieve greatness if they work hard enough, Hambrick said there is a “silver lining” to the research.

“If people are given an accurate assessment of their abilities and the likelihood of achieving certain goals given those abilities,” he said, “they may gravitate toward domains in which they have a realistic chance of becoming an expert through deliberate practice.”

Filed under deliberate practice expertise working memory performance psychology neuroscience science

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